A Trial of Hepatic Arterial Infusion Combined With Bevacizumab and Sintilimab for Unresectable A-staged Hepatocellular Carcinoma in BCLC Classification (D-TRIPLET)

NCT05214339 | Unknown Phase 2 DMC

• 1 other identifier: D-TRIPLET
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

This study was designed to evaluate the effectiveness and safety of hepatic arterial infusion chemotherapy combined with Bevacizumab and Sintilimab (Triplet-combined Therapy) for Unresectable A-staged Hepatocellular Carcinoma in BCLC classification. The primary outcome measure is to evaluate the objective response rate (ORR RECIST 1.1) of Triplet-combined Therapy for Unresectable A-staged Hepatocellular Carcinoma in BCLC classification. The secondary Outcome measures include the objective response rate (ORR mRECIST 1.1), duration of response (DOR), disease control rate (DCR), progression-free survival rate (PFSR) \[ Time Frame: 6- and 12-month\], overall survival rate (OSR) \[ Time Frame: 6- and 12-month\], the median progression-free survival time (mPFS) and median overall survival time (mOS) of Triplet-combined Therapy for Unresectable A-staged Hepatocellular Carcinoma in BCLC classification. Moreover, this study aims to assess the safety and tolerability of Triplet-combined Therapy for Unresectable A-staged Hepatocellular Carcinoma in BCLC classification.

Conditions

Unresectable Hepatocellular Carcinoma; Hepatocellular Carcinoma by BCLC Stage

Keywords

Unresectable Hepatocellular Carcinoma; hepatic arterial infusion chemotherapy; Bevacizumab; Sintilimab

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) by RECIST 1.1

  ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1

  From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 3 years)

Secondary Outcomes (9)

• Objective response rate (ORR) by mRECIST

  From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 3 years)

• The disease control rate (DCR)

  From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 3 years)

• Duration of response (DOR) by RECIST 1.1 and mRECIST

  From the first documentation of CR or PR to the first date of documentation of disease progression or death whichever occurs first (up to approximately 3 years)

• The progression-free survival rate (PFSR) by RECIST 1.1 and mRECIST

  From date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first (up to approximately 3 years)

• The overall survival rate (OSR)

  From date of first dose of study drug to the date of first documentation of death from any cause, whichever occurs first (up to approximately 3 years)

Study Arms (1)

TRIPLET

EXPERIMENTAL

Combination Product: Hepatic Arterial Infusion combined with Bevacizumab and Sintilimab Drug: FOLFOX Protocol (Oxaliplatin, fluorouracil, and leucovorin); Bevacizumab and Sintilimab for injection. Procedure: 1. On the first day of treatment, HAIC was conducted through a catheter intubated into the tumor feeding artery under DSA guidance with the following chemotherapeutic drugs (mFOLFOX7, oxaliplatin 85 mg/m2 2 hours, folinic acid 400 mg/m2, 5-FU 2500 mg/m2 46 hours) pumped into the tumor artery. The HAIC is repeated every 3 weeks. The cumulative maximum sessions of HAIC is up to 6 times. 2. Intravenous infusion of Bevacizumab 7.5mg/kg every 3 weeks on the 4th day. 3. On the 25nd day of treatment, namely the second session of HAIC, intravenous infusion of Sintilimab 200mg every 3 weeks. 4. The cumulative maximum drug use period is up to 1 years. The patient is concurrent on medication until the treatment discontinuation criteria specified in the protocol appear.

Drug: Hepatic Arterial Infusion(mFOLFOX7) combined with Bevacizumab and Sintilimab

Interventions

Hepatic Arterial Infusion(mFOLFOX7) combined with Bevacizumab and Sintilimab DRUG

The patient will receive Hepatic Arterial Infusion(mFOLFOX7) on the first day, and intravenous infusion of Bevacizumab on the 4th day, and intravenous infusion of Sintilimab on the 25th day. The intervention is repeated every 3 weeks.

TRIPLET

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient voluntarily joins the study and signs an informed consent;
• Age≥18 years old, ≤70 years old, both men and women;
• Clinical or pathologically confirmed unresectable BCLC A-stage hepatocellular carcinoma, no further anti-tumor treatment;
• Child-Pugh score small or equal to 6 points (Child-Pugh A-B);
• ECOG score: 0 to 1 (according to the ECOG score classification);
• The expected survival is longer than 12 weeks;
• The laboratory parameters meets the following requirements (no blood components and cell growth factors are allowed within 14 days before the first dose):
• Absolute neutrophil count≥3.0×109 / L;
• Platelets≥80×109 / L;
• Hemoglobin≥90 g / L;
• serum albumin≥28 g / L;
• Thyroid stimulating hormone (TSH)≤1×ULN (if abnormalities should be considered at the same time FT3, FT4 levels, patients with FT3 and FT4 levels in normal range can also be enrolled);
• bilirubin≤1.5×ULN (within 7 days prior to the first dose);
• ALT≤3 x ULN and AST≤3 x ULN (within 7 days prior to the first dose);
• AKP≤2.5×ULN; serum creatinine≤1.5×ULN;

You may not qualify if:

• The patient has any active auto-immune disease or a history of autoimmune disease (such as the following, but not limited to: auto-immune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroid hyperfunction; patients with vitiligo. For patient with history of asthma, complete remission of asthma in childhood without any intervention after adulthood can be included, while those asthma patients who require bronchodilators for medical intervention cannot be included.);
• The patient is using immunosuppressive agents or systemic hormonal therapy for immunosuppression purposes (dose \> 10 mg/day of prednisone or other therapeutic hormones) and continues to be used within 2 weeks prior to enrollment;
• Severe allergic reactions to other monoclonal antibodies;
• Known for a history of central nervous system metastasis or hepatic encephalopathy;
• Having a history of organ transplantation;
• Patients with clinically symptomatic ascites who require puncture, drainage, or ascites drainage within 3 months, except for those who have a small amount of ascites but no clinical symptoms;
• Suffering from hypertension, and cannot be well controlled by antihypertensive drugs (systolic blood pressure≥140mmHg or diastolic blood pressure≥90 mmHg);
• Suffering heart diseases with clinical symptoms or those not well controlled, such as: (1) heart failure in NYHA class 2 or higher; (2) unstable angina; (3) myocardial infarction occurred within 1 year; (4) clinically symptomatic supraventricular or ventricular arrhythmia requiring treatment or intervention; (5) Tc \> 450ms (male); Tc \> 470ms (female);
• Coagulation dysfunction (INR\>2.0, PT\>16s), bleeding tendency or receiving thrombolysis or anticoagulant therapy, allowing prophylactic use of low-dose aspirin or low molecular heparin;
• There are significant clinically significant bleeding symptoms or clear bleeding tendency within 3 months before enrollment, such as hemoptysis of 2.5ml or more per day, gastrointestinal bleeding, esophageal varices with bleeding risk, hemorrhagic gastric ulcer or vasculitis, etc. If the fecal occult blood is positive in the baseline period, it can be watched, then gastroscope is needed for those fecal occult blood is still positive. If the gastroscope indicates severe esophageal varices, it cannot be enrolled, except for those who have undergone gastroscopy within a month or less to exclude such cases);
• Events of arterial/venous thrombosis occurring within the first 6 months of enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
• There are known hereditary or acquired bleeding and thrombophilia (such as hemophilia patients, coagulopathy, thrombocytopenia, etc.);
• Urine routine indicates that urine protein≥++ and 24-hour urine protein amount \> 1.0g was confirmed;
• The patient has active infection, unexplained fever (≥38.5°C) within 3 days before administration, or baseline white blood cell count\>15×109/L;15 Patients with congenital or acquired immunodeficiency (such as HIVinfected patients);
• HBV-DNA\>2000 IU/ml (or 104 copies/ml); or HCV-RNA\>103 copies/ml; or HBsAg+ and anti-HCV antibody positive patients;

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Third Affiliated Hospital, Sun Yat-Sen University: collaborator
• Nanfang Hospital, Southern Medical University: collaborator
• Xiangya Hospital of Central South University: collaborator

Study Sites (5)

Yang-Kui Gu

Guangzhou, Guangdong, 510060, China

RECRUITING

Sun Yat-Sen Memorial Hospital

Guangzhou, Guangdong, 510120, China

NOT YET RECRUITING

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510510, China

NOT YET RECRUITING

The Third Affiliated Hospital of Sun Yat-Sen University

Guanzhou, Guangdong, 510630, China

NOT YET RECRUITING

Xiangya Hospital of Central South University

Changsha, Hunan, 410013, China

NOT YET RECRUITING

MeSH Terms

Interventions

Bevacizumab; sintilimab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Yang-Kui Gu, Prof.

CONTACT

+862087345272; guyk@sysucc.org.cn

Meng-Xuan Zuo, Dr.

CONTACT

zuomx@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 30, 2021
• First Posted: January 28, 2022
• Study Start: March 16, 2022
• Primary Completion: January 1, 2023
• Study Completion: June 1, 2023
• Last Updated: May 5, 2022

Record last verified: 2022-05

Locations

CN (5)